A5. Drugs in liver diseases Flashcards
UK drinking guidelines?
-To keep health risks from alcohol to a low level it is safest not to
drink more than 14 units a week on a regular basis.
-If you regularly drink as much as 14 units per week, it is best to
spread your drinking evenly over 3 or more days.
-1 unit = 10mL pure ethanol = amount of alcohol average adult can
process in an hour
-Community pharmacies ideally located to increase awareness and
allow for signposting
Alcohol withdrawal symptoms?
one note
If alcohol withdrawal is not managed promptly?
-risk of seizures, delirium tremens &
Wernicke’s encephalopathy
-Cases can be complicated by mental health illness, vulnerability, lack
of social support and other co-morbidities
what is Delirium tremens?
severe disorientation, increased HR & BP, breathing issues, uncontrollable restless behaviour
NICE guidance for alcohol withdrawal?
-Prescribe a benzodiazepine (chlordiazepoxide or diazepam)
-At a fixed-dose regimen or symptom-triggered regimen
-Reducing the dose to zero over 7–10 days
what is Wernicke’s Encephalopathy?
Definition: acute confusion, psychosis, ataxia (poor muscle control) and
oculomotor dysfunction
How does Wernicke’s Encephalopathy occur?
Occurs due to lack of thiamine (vitamin B1), often complication of high alcohol
intake
Treatment of Wernicke’s Encephalopathy
-Parenteral thiamine, followed by oral thiamine, should be given to patients
with suspected Wernicke’s encephalopathy, those who are malnourished or at
risk of malnourishment, those who have decompensated liver disease or who
are attending hospital for acute treatment.
-Prophylactic oral thiamine should also be given to harmful or dependent
drinkers if they are in acute withdrawal, or before and during assisted alcohol
withdrawal.
-Often given alongside multivitamins
hepatic circulation structure?
one note
Liver function tests?
one note
Describe aminotransferases (ALT and AST)
-Levels used to detect damage to hepatocytes (often known as
hepatocellular damage) → liver injury
-Transferases are intracellular enzymes present in hepatocytes
-Hepatocytes are present in the liver parenchyma which is the functional
component on the liver, they help to filter blood & remove toxins
-Hepatocytes will release enzymes ALT & AST when they are
damaged/injured by alcohol, drug exposure, a virus or in non-alcohol fatty
liver disease
-ALT is more specific than AST (think L for liver!)
-Very high levels of ALT (up to several thousand) in acute injury
-Levels usually not as high in chronic hepatitis
Describe alkaline phosphatase (ALP)
-Levels used to detect cholestasis
- Also present in bone cells so non-specific.
-If ALP raised, but not clear whether this is due to liver or bone disease, then should be looked at in conjunction with other LFT results.
what is cholestasis?
-Flow of bile from liver is reduced or blocked (e.g. by a gallstone)
-Often an indicator of bile obstruction
Describe Gamma Glutamyl Transferase (GGT)
-Enzyme released in all types of liver
dysfunction (difficult to use for
differentiation)
-Fairly specific marker though (95%
due to liver isoenzyme)
-Raised GGT with a raised ALP or
bilirubin = Cholestatic damage
-Raised GGT in isolation = Alcohol
Abuse or Enzyme-Inducing Drugs
-Levels can be up to 20 times the
upper limit of normal
Describe bilirubin
-Produced by the destruction of red blood cells
-Non-specific for liver injury, also released in haemolytic anaemias
-Serum bilirubin in excess of 50 micromol/L can produce jaundice in adults
-Seen in hepatic damage, decreased metabolism of unconjugated bilirubin
-Also seen if a cholestatic cause is likely, ALP & GGT will also be raised,
indicating post-hepatic obstruction
Describe Albumin
-Liver is responsible for manufacture of plasma proteins
-Albumin is a marker of synthetic function of the liver
-Acts as a hepatocellular marker
-Non-specific as low in malnourished patients or those with nephrotic
syndrome
-Albumin has a half-life of about 20 days, so is an indicator of chronic
rather than acute liver disease
-Unusual to see high levels of albumin in acute liver injury
Clotting Indicators (INR & Prothrombin)?
-INR = International Normalised Ratio (might have heard of this before from
warfarin monitoring)
-Ratio of a patient’s prothrombin time compared to a control
-Liver is responsible for production of vitamin K-dependent clotting factors
-If INR increases = synthetic function of liver decreased OR absorption of vitamin K impaired
-However, non-specific as if patient on vitamin K antagonist e.g. warfarin, or patient has coagulopathy disorders may also be deranged
-Changes in prothrombin time occur more rapidly than changes in albumin so more useful in predicting hepatocellular damage in acute situations
classifications of liver diseases?
-Acute and chronic (chronic >6 months)
-Cirrhosis (Hepatic)
-Compensated and decompensated
-Cholestasis → impaired bile flow (can be intrahepatic or extrahepatic)
ONE NOTE
Liver function test summary?
-Don’t look at individual results in isolation, look at their trend,
alongside the other LFTs.
- Enzymes – is it damaged?
-Bilirubin and ALP – is it secreting or is there a blockage?
-Albumin and clotting – is it working?
Child-Pugh Score?
ONE NOTE
Describe the child-pugh score
-Can be used to assess the severity of chronic liver disease, but no indication
about metabolic capacity
-Each of 5 parameters is given a score – ascites, encephalopathy, nutritional
status, albumin and bilirubin
-The total score is then converted to a grade A, B or C – with C representing the most advanced disease
-Occasionally drug SPCs will recommend that dosing is based on Child-Pugh score/grade
